Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter

Jung Min Kim, Shenping Wu, Thomas M. Tomasiak, Claudia Mergel, Michael B. Winter, Sebastian B. Stiller, Yaneth Robles-Colmanares, Robert M. Stroud, Robert Tampé, Charles S. Craik, Yifan Cheng

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

ATP-binding cassette (ABC) transporters translocate substrates across cellmembranes, using energyharnessed fromATPbinding andhydrolysis at their nucleotide-bindingdomains1,2.ABCexporters are present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, aswell as inmany human diseases3,4.TmrABis a heterodimericABCexporter fromthe thermophilic Gram-negative eubacterium Thermus thermophilus; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif5. Here we report a subnanometre-resolution structure of detergent-solubilizedTmrABin a nucleotide-free, inward-facing conformation by single-particle electron cryomicroscopy. The reconstructions clearly resolve characteristic features ofABCtransporters, including helices in the transmembrane domain and nucleotidebinding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as fromthe cytoplasm,indicating that the transporter lies in an inwardfacing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Furthermore, comparison between our structure and the crystal structures of other ABC transporters suggests a possible trajectory of conformational changes that involves a sliding and rotatingmotion between the two nucleotide-bindingdomains during the transition from the inwardfacing to outward-facing conformations.

Original languageEnglish (US)
Pages (from-to)396-400
Number of pages5
JournalNature
Volume517
Issue number7534
DOIs
StatePublished - Jan 15 2015
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter'. Together they form a unique fingerprint.

Cite this